Anybody have a link to a database of medicines and supplements and their experimentally-verified ability to treat/reverse mild cognitive impairment (MCI) and ALZ? There are several books out there claiming success, but they spend a lot of time on anecdotal accounts and the literature cited often isn't much better. I also have a hard time finding the few cited articles that, according to their titles, appear that they could be good experimental designs that would actually prove something.

I am under "integrative medicine" treatment with supplementation (not prescriptions) and dietary augmentation/restriction (no grains, sugar, dairy, etc.), but am getting increasingly skeptical. I'd like to see the research or at least an objective review of what I'm taking to justify the substantial expense and inconvenience of 31 pills/day.

Below are links to the studies in which certain natural products have produced initial improvements in cognition that were sustained in early to moderate Alzheimer's disease. None of these studies used a placebo but that is not a major design error as the slope of decline in individuals with Alzheimer's disease taking a placebo has been well established. If a person with mild cognitive impairment or Alzheimer's disease improves while taking a placebo either the placebo has a compound in it that is doing some good or the person is taking some kind of medication or supplement that is producing at least a temporary beneficial effect.

None of these trials and studies were randomized which could be a problem as people progress at different rates early in Alzheimer's disease and randomization would eliminate this compounding factor. None of them are double-blinded which is a bigger problem as the observer may consciously or sub-consciously produce biased results.

Having said all that I am tired of all the people who say these trials and studies are useless or garbage. This is often a reflection of their bias against the use of supplements to treat mild cognitive impairment and Alzheimer's disease. Oxidants (especially peroxynitrite) produce widespread damage in the hippocampus and cortex in Alzheimer's disease and some of that damage can be reversed with particularly strong antioxidants. For example, the regrowth of neurons can be restarted in the hippocampus and improving acetylcholine levels in the hippocampus can lead to improvements in certain forms of memory (object recognition, facial recognition, recognition of places, for instance). The trial results fit (although not prove) the hypothesis and vice versa. This is very difficult for some people to accept because they adhere to the belief that Alzheimer's disease is a highly complicated disease for which nothing can be done.

Here are the trials and studies.

Aromatherapy using rosemary and lemon in the morning for cognition and lavender and orange in the evening for relaxation using a diffuser (direct inhalation of clove and bay laurel in the morning may work better, although increased anxiety can occur with clove)

I should add some of the rationale behind diet in the treatment of mild cognitive impairment and Alzheimer's disease. Carbohydrates and sugar increase levels of myo-inositol in the brain which is linked to an increased conversion rate from mild cognitive impairment to Alzheimer's disease.

Myo-Inositol, N-Acetylaspartate Are Sensitive Biomarkers for Conversion From MCI to Alzheimer's Disease

Comparison of patients with progressive disease versus those who developed AD for the cingulate gyrus showed the increased myo-inositol-to-water ratio to be 72% predictive for dementia; similarly for the hippocampus, it was 70% predictive for dementia.

The polyphenols in spices, vegetables, fruits, etc. in particular diets (such as a Mediterranean diet or a diet from India) both scavenge peroxynitrite and repair part of the damage that it does to the brain.

Defenses against peroxynitrite: selenocompounds and flavonoids.

Abstract

The inflammatory mediator peroxynitrite, when generated in excess, may damage cells by oxidizing and nitrating cellular components. Defense against this reactive species may be at the level of prevention of the formation of peroxynitrite, at the level of interception, or at the level of repair of damage caused by peroxynitrite. Several selenocompounds serve this purpose and include selenoproteins such as glutathione peroxidase (GPx), selenoprotein P and thioredoxin reductase, or low-molecular-weight substances such as ebselen. Further, flavonoids, such as (-)-epicatechin, which occurs in green tea or cocoa as monomer or in the form of oligomers, can contribute to cellular defense against peroxynitrite.

Suppression of the nuclear factor-kappaB activation pathway by spice-derived phytochemicals: reasoning for seasoning.

Abstract

The activation of nuclear transcription factor kappaB has now been linked with a variety of inflammatory diseases, including cancer, atherosclerosis, myocardial infarction, diabetes, allergy, asthma, arthritis, Crohn's disease, multiple sclerosis, Alzheimer's disease, osteoporosis, psoriasis, septic shock, and AIDS. Extensive research in the last few years has shown that the pathway that activates this transcription factor can be interrupted by phytochemicals derived from spices such as turmeric (curcumin), red pepper (capsaicin), cloves (eugenol), ginger (gingerol), cumin, anise, and fennel (anethol), basil and rosemary (ursolic acid), garlic (diallyl sulfide, S-allylmercaptocysteine, ajoene), and pomegranate (ellagic acid). For the first time, therefore, research provides "reasoning for seasoning."

Mediterranean Diet and Risk for Alzheimer’s Disease

Results

There were 262 incident AD cases during the course of 4 (±3.0; range, 0.2–13.9) years of follow-up. Higher adherence to the MeDi was associated with lower risk for AD (hazard ratio, 0.91; 95% confidence interval, 0.83–0.98; p = 0.015). Compared with subjects in the lowest MeDi tertile, subjects in the middle MeDi tertile had a hazard ratio of 0.85 (95% confidence interval, 0.63–1.16) and those at the highest tertile had a hazard ratio of 0.60 (95% confidence interval, 0.42–0.87) for AD (p for trend = 0.007).

Interpretation

We conclude that higher adherence to the MeDi is associated with a reduction in risk for AD.

Mediterranean diet and Alzheimer disease mortality

Eighty-five patients with AD (44%) died during the course of 4.4 (±3.6, 0.2 to 13.6) years of follow-up. In unadjusted models, higher adherence to MeDi was associated with lower mortality risk (for each additional MeDi point hazard ratio 0.79; 95% CI 0.69 to 0.91; p = 0.001). This result remained significant after controlling for all covariates (0.76; 0.65 to 0.89; p = 0.001). In adjusted models, as compared with AD patients at the lowest MeDi adherence fertile, those at the middle fertile had lower mortality risk (0.65; 0.38 to 1.09; 1.33 years’ longer survival), whereas subjects at the highest fertile had an even lower risk (0.27; 0.10 to 0.69; 3.91 years’ longer survival; p for trend = 0.003).

Conclusion

Adherence to the Mediterranean diet (MeDi) may affect not only risk for Alzheimer disease (AD) but also subsequent disease course: Higher adherence to the MeDi is associated with lower mortality in AD. The gradual reduction in mortality risk for higher MeDi adherence tertiles suggests a possible dose–response effect.

The answers are not easy and they are not complete, but the idea that we know nothing about Alzheimer's disease or how to treat it is not a reflection of reality

I am impressed by this clinical trial. It was a randomized, double-blinded, placebo controlled studies. The botanicals used affected many of the mechanisms that are involved in Alzheimer's disease and appeared to stabilze the disease for at least one year. Thank you for posting . I hope that you don't mind me reposting it elsewhere.

Lane, why don't you investigate the source and methods before you endorse a clinical trial.

This is not a legitimate clinical trial for the following reasons.

1. There is no government supervision of any kind, not from the FDA, the Canadian government, the EU, or any other government. No legitimate institution such as a university or medical center is envolved. A company run clinical trial is practically guaranteed to get positive results. In fact we don't even know if any trial was actually done. The company could just have created the paperwork and submitted it.

2. What legitimate clinical trial would test a medication with seven active ingredients? How would you know which ingredient is effective and which ingredient causes side effects. Furthermore there is no listing of side effects.

3. Imedpub.com, the publisher of this so-called clinical trial, is headquartered in Hyderabad, India, and was sued by the Federal Trial Commission in 2016 for deceiving academics and researchers, falsifying information in clinical trial papers and hiding publication fees. This company will publish just about anything for the right price.

This is not a legitimate clinical trial, but rather a marketing ploy by the American corporation Genescient, using a discredited Indian medical publishing company.

Now some do have a personal stake in the results, but no more so than researchers at pharmaceutical companies. Furthermore, the clinical trial was placebo controlled (although relying in the end on historical rates of decline in other placebo controlled trials), randomized and double-blinded.

The seven active ingredients were chosen based on a drosophila model to find the ones that had the greatest impact on pathways associated with Alzheimer's disease. The positive compounding effect of antioxidants may have their limits, but the expectation that a combination of antioxidants is sometimes more effective than one is not baseless.

The journal in which the study was published does not automatically invalidate the results (although it does provide fodder for those who wish to criticize the results). Good studies have been published in "bad" journals and bad studies have been published in "good" journals.

Finally several other clinical trials using a similar approach have produced similar results.

A 24-week randomized open-label study with Korean red ginseng (KRG) showed cognitive benefits in patients with Alzheimer’s disease. To further determine long-term effect of KRG, the subjects were recruited to be followed up to 2 yr. Cognitive function was evaluated every 12 wk using the Alzheimer’s Disease Assessment Scale (ADAS) and the Korean version of the Mini Mental Status Examination (K-MMSE) with the maintaining dose of 4.5 g or 9.0 g KRG per d. At 24 wk, there had been a significant improvement in KRG-treated groups. In the long-term evaluation of the efficacy of KRG after 24 wk, the improved MMSE score remained without significant decline at the 48th and 96th wk. ADAS-cog showed similar findings. Maximum improvement was found around week 24. In conclusion, the effect of KRG on cognitive functions was sustained for 2 yr follow-up, indicating feasible efficacies of long-term follow-up for Alzheimer’s disease.

Compared to CT [conventional therapy] alone, CT + H [conventional therapy plus herbs] significantly benefited AD patients. A symptomatic effect of CT + H was more pronounced with time. Cognitive decline was substantially decelerated in patients with moderate severity, while the cognitive function was largely stabilized in patients with mild severity over two years. These results imply that Chinese herbal medicines may provide an alternative and additive treatment for AD.

Now there are always those prone by instinct to doubt all of these results either because they have another dog in the hunt, because they don't believe natural products can treat anything, or because they simply doubt any results unless verified time and time again.

This remains my favorite quote on Alzheimer's disease (all of the botanicals tested in the clinical trials above are peroxynitrite scavengers).

"Clinical trials with over-the counter supplements have concentrated either on items which suppress inflammation, or on antioxidants which scavenger oxygen derived free radicals. Most of these items have proved to be worthless in the treatment of Alzheimer's disease. Similarly most drugs used to treat Alzheimer's disease do little to slow the deterioration, but instead offer a mild temporary symptom relief. However, evidence has been accumulating that the primary driver of Alzheimer's disease is a nitrogen derived free radical called peroxynitrite, which may mediate both amyloid and tau accumulation as well as their toxicity. Excellent results have been obtained with peroxynitrite scavengers, with reversals of Alzheimer's disease in human clinical trials being repeatedly demonstrated. IMHO, the only thing which may be preventing the abolition of Alzheimer's disease is the mental inertia of scientists, as well as the bureaucrats who fund them. Unfortunately, most bureaucrats keep throwing money into repeatedly testing discredited interventions, while ignoring successful ones. Common sense is anything but....

Sorry, I've been away for a while... No, don't mind at all if you repost(ed) my link - if this is as good as it seems, it would be to everyone's benefit to know about it.

I might have been off the discussion boards for a couple of weeks, but I have been keeping tabs on this Geneaire Rebuilder. My interest in it is more for a family member who has recently been diagnosed w/ early stage dementia. I'm not a fan of pharmaceuticals (most seem to create more problems than they're supposed to fix), so I've been looking for all types of alternatives - that's how I came across this one.

They have a website and more publications have since come out, including this white paper - http://geneaire.com/wp-content/uploads/2018/10/Geneaire-ReBuilder-White-Paper-Oct-2018.pdf - which goes into greater detail on how much of their research has relied on Methuselah Flies and continued genome analysis w/ regards to the compounds being used.

I also must confess, I decided to give it a try - it just became available on Amazon... Getting one for my uncle, and -- since it is just as much a preventative -- one for myself. We'll see if it makes a difference.

As you were mistakenly diagnosed - you understand I strongly wish to avoid such mistakes myself. No doubt your first doctors were experienced and smart. Yet not half as smart as the doctor who later accurately diagnosed you.

As yet I have found no neurologist able to diagnose the cause of my dementia.

I need someone bright enough to do a differential diagnosis - BEFORE this gets worse.

I live in Miami - I will travel - but exactly who can I trust to provide an accurate diagnosis?

I am confident you have discovered some of the best neurologists in the world. Unless it violates board rules (Private or Public) you would be profoundly helpful to me if you would share the best that you know - still taking on patients?

With new studies coming out daily - I highly recommend visiting PubMed.

I search for every antioxidant that may cross the BBB.

You could not be more correct about the inflammatory response. (My father was a dentist I did not get along with - so I have never been to one.) Guess what else is strongly associated with Alzheimer's, Cardiovascular (and countless other diseases?) Gingivitis. I will in short order get this treated and fixed!

I also run searches on anything that might inhibit M-Tor.

Next I look for anything that raises growth factors in the brain.

Finally - find any product that inhibits GSK-3.

One thing I avoid are supplements with choline. For reasons not yet understood - but likely related to gut bacteria supplements such as phosphatidylcholine are too often metabolized into a very toxic substance known as trimethylamine N-oxide or (TMAO).

So, there is a very likely chance that the Acetyl N Carnitine I am giving to DH (and considering taking myself) is being converted to TMAO and therefore is toxic?

In DH, the Acetyl N Carnitine brings on an increased responsiveness and a happier demeanor. He has been taking this supplement for one year. I have seen what I would classify as only a slight decrease in mental (thinking) symptoms (stabilizing?)—all of which could just be normal for his stage/age. So I am reluctant to stop this supplement for him.

I purchased phosphtidylcholine (new) and notice that when I take this one the area surrounding my liver hurts. The reason I purchased the supplement in the first place was due to the claim that this substance protects the liver. My surprise diagnosis for my health is”fatty liver.” I may not take this one any more. I won’t be giving DH this supplement for sure. He is a smoker and doesn’t need more toxins.

I use my neurologist recommended Ashwanda, Bicopa and Virgin coconut oil supplements. They are all natural, have no side effects and seems to measurably help with cognitive decline. I use them daily and won’t stop. They are important in my Alzheimer’s treatment regimen.

I am also trying to get in an Alzheimer’s seizure medication trial if I can find one. This shows real promise to control cognitive decline in Alzheimer’s patients. READ THIS;

Are any clinical trials in the following subject area available? This is curroas of March 2019 and serotonin offer great promise.

PLEASE READ THIS IN ITS ENTIRETY:

This is the most current research of Alzheimer’s and seizures I could find (March 2019) a few weeks ago from Baylor Medical School. It is comprehensive and excellent. It’s important to “read all of it.” Especially pay attention to the treatment part toward the end and the very end where they think seizure treatment might even control the progression of Alzheimer’s. Here is the link:

Rich, i agree with you about the use of supplements and vitamins. My NEUROLOGIST recommended Gingseng and Gingko when i got diagnosed with Early Onset Dementia. I tried the gingseng and had GREAT RESULTS! It lifted the dark, black cloud surrounding my thought processes. It did not get rid of my communication boo-boos, but the brain fog is definitely lifted!

I would recommend people at least try the gingseng AFTER checking with their doctor to make sure the supplement does NOT interfere with any of their medications! To me, at least tryimg something is worth a chance, even if it is just a temporary improvement! People with dementias, hav a finite time to live, so i want to hav as much quality time i can get while still on this earth.

I did not try the gingko yet as im waiting until my dementia progresses....

Lane, THANK YOU SO MUCH for the information u provided! I hav been reading EVERYTHIMG i can get my hands on about dementia. My philosophy is that knowledge is golden!

I found some information about each one of the things u mentioned, so am excited to read your listings! With the dementias being SO COMPLICATED, my beliuef is that the cure will need to address several aspects of the disease, especially sinc the brain is the most complicated organ in the human body!

I truly believe that carbs and sugars affect the brain, so diet and exerciae is crucial for the brain, even just a LITTLE BIT of CHANGE in our lives can help!

I aslo hav experienced a decline in my cognitive function when im stressed out. I was an avid promoter of therapeutic massage BEFORE my diagnosis, and know HOW MUCH it de-stresses our body and mind! It also helpos eliminate TOXINS in the body of a person who drinks LOTS of water aftewr the massage to flush out those circulating toxins!

I know how MUCH i was stressed for several months after i received my diagnosis. I was full of fear and anxiety about my future, and once i got a MASSAGE (and started counselling and antidepressants), my stress level declined! It also rekaxed my tightened muscles from all the anxiety! I highly recommend EVERYONE try a therapeutic massage!

I have not previously commented on issues relating to treatment, etc. other than to warn members of using supplements that have not been tested by recognized organizations that test for purity, ingredient percentages, etc.

A supplement that does not have a USP (United States Pharmacopoeia) verified insignia or NSF (National Sanitation Foundation) insignia must be avoided because there is no way for the user to know if the supplement contains toxic substances, any of the advertised supplement, etc. Supplements are not regulated by the FDA like pharmaceuticals are.

Manufacturers do not have to follow good manufacturing principles. Anyone can market a supplement based on any truth but most likely falsehood or misrepresentation of published studies.

My input here is going a big step further because I am terribly concerned about the deceptions proffered in the study referenced in this thread, the journal reputation, the authors listed and the publishing company. Larry the Runner is absolutely correct in his comment about the “badness” of the work and the journal.

Interestingly the company that published the journal was basically shutdown by a Nevada court ruling last week for deceptive practices in publication, peer review, conclusions, etc. in a lawsuit filed by the Federal Trade Commission. They were also fined $50 million. Not a slap on the wrist and contrary to Lane’s comments about good journals publishing bad stuff there is no comparison. Simply put, the journal is a SHAM, the company is a criminal enterprise. https://www.courthousenews.com/wp-content/uploads/2019/04/Publishing.pdf

I was not expecting such a timely outcome that I could use to support my assessment but after digging through 6 layers of google pages I found the lawsuit, Had I given up the harm to our community could/would continue.

It is not my intention to dash any hopes. I do not want my e-villagers to endure more suffering. If I can help in that I will. My sweetie died 3 years ago from Normal Pressure Hydrocephalus but I continue to monitor the site and jump in when I see dangerous information spreading in my beloved community.

I started my investigation by looking up the UC Irvine authors in the paper to see if their official webpages supported the information in the study. First red flag - NO it did not.

In fact the author Shankar has a dementia clinic in CA. His treatment webpage explicitly endorses solely the FDA approved pharmaceuticals for Alzheimer’s care. There is absolutely no mention of the Geneaire Company, no mention of this article, etc. I will link the site in a separate don’t lose this one by toggling over.

I didn’t delve too much into the other author who is an emeritus physicist. The Shankar info was sufficient to stop that line of further inquiry.

Please my dear e-villagers - do not take any supplements (even standard ones (Bs, Cs, Ds, etc) if the labels do not indicate USP or NSF verified/certification. It might be slightly more expensive but the likelihood that you are ingesting what is advertised is significantly higher than a product without those insignias and you can be assured that there is nothing toxic as a byproduct, deliberate ingredient, or accidental one.

Treatment of cognitive impairment should be based on the underlying medical conditions. Therefore, it is very important to obtain an accurate diagnosis.

In the case of Alzheimer’s disease (AD), contrary to general belief, currently available pharmacologic treatments are not only beneficial, but also in many cases, delay disease progression for 2 to 6 years. Combining these pharmacologic treatments with other types of treatments brings the maximum benefits to the patients. Other types of treatment include:

Over-the-counter medications and supplements

Cognitive, occupational and speech therapies

Cognitive Exercise

Physical Exercise

Social Activity

Caregiver Support

Proper structuring of the daily routine and good care management

Today there are five FDA-approved medications for treatment of AD (e.g. Cognex® (tacrine), Aricept® (donepezil), Razzadyne® (galantamine), Exelon® (rivastigmine) and Namenda® (memantine)) and all of them have shown positive treatment outcomes in long-term studies.

Just another confirmation of the scandalous practices of the Journal owner:

Regarding diagnosis. I think the best advise has been frequently stated by member Mimi which is to locate a University with a dementia studies department. I’m sure there are options in FL. One problem that most experience is a long time to get an appointment.

I will do some research on possible options and post a bit later.

Here’s a link to alz.org page about the various extensive medical tests that need to be done to get a diagnosis of dementia and to rule out dementia by finding a treatable cause for symptoms.

The gut is so important in total health. If one has a leaky gut, particles from the food we eat leave the gut and get into the bloodstream and go to various places in the body, including the brain, and antibodies are formed. Leaky gut and poor microbiome (types of bacteria in your gut) have been said to perhaps be the "cause" of autoimmune diseases. Fix your leaky gut, fix your microbiome and health will improve. How do you heal these? Primarily through diet.

The above is an over-simplification. If you wish to explore this further, there are books on Amazon, youtube videos, etc. Dr Tom O'Bryan was a triathlete in his 40s when he had blood tests that showed he had antibodies to his myelin sheath, cerebellum and one other part of his brain/nervous system. He has since healed this through supporting his microbiome. More details here: https://www.youtube.com/watch?v=Bqn51KtCJr0 and he has written a book called "The Autoimmune Fix."

Other "pioneers" in knowledge of the microbiome are Dr Mark Hyman, Pedram Shojai, Dr. Robynne Chutkan and others.

My name is Kennedy Matsagas, and I am one of the author-researchers of the Geneaire ReBuilder Paper.

I
am truly very appreciative of your concern, and your desire to help and
protect the dementia community from scams and ineffective treatments.
As the daughter of a Lewy Body sufferer myself, I know the value in
being hyper-aware of what options exist, and separating facts from
fiction.

I wanted to address some of the points you made in your
post. First, the human pilot was overseen by neurologist Dr. William
Shankle of the Shankle Clinic and Dr. Cristina Rizza, a cardiologist and
aging researcher. The pilot was monitored by an FDA-approved
Institutional Review Board (IRB), and is registered on
ClinicalTrials.gov. While Dr. Shankle does not specifically mention
Geneaire ReBuilder on his website, he has reccomended the supplement to
over 200 of his patients, and many of his patients who participated in
the original pilot are still taking Geneaire ReBuilder today.

Second, the UCI affiliated authors were involved in developing the Drosophila animal
model that was used by Genescient to develop this supplement over the
course of 10 years. This is why the UCI authors do not mention Geneaire
on their websites, they were responsible for the flies that the research
is based on.

Third, Geneaire ReBuilder is manufactured for
Geneaire by a
National Sanitation Foundation (NSF) certified facility, which also
happens to be used by many other large supplement distributors in
the United States.

Finally, it was the decision of the
Genescient Board of directors to publish the work in the Journal of
Clinical Medicine and Therapeutics, an iMed publication. We have
published with other iMed journals in the past, and so have other
academic and corporate researchers that we are acquainted with. We were
not aware of the ethical concerns surrounding the journal at the time
of publication.

If you, or anyone else, has any more
questions or concerns about Genescient's publications and research, I am
more than happy to answer them to the best of my ability.

Thank you for taking the time to come explain more about the company, its product, and its studies. Do you have any more updates?

I am afraid too many inferences are made to try to "tarnish" results for various antioxidant herbs in the treatment of Alzheimer's disease. That does not mean that the concerns are automatically invalid or wrong, but they often confuse people into thinking that the results have to be invalid. This delays progress into finding treatments that may actually help people with Alzheimer's disease.

I have had some discussions with Kennedy regarding this and I do think she's amazing. It would probably not be appropriate for either her, the company she works for, or the company I am president of, to post updates here because that could appear to be self-promotion.

Agent99 and LarryTheRunner have my respect because they are genuinely trying to protect those who may be vulnerable from scams and hype. I see tens of millions of dollars a year being spent on advertising of supplements that have no science-based research behind them. Obviously, when I made a career decision to become significantly involved, I did a lot of research and met with a lot of researchers. In my case, this also meant meeting with Dr. Shankle and with patients and caregivers.

For updates, my suggestion is to do your Google searches and try to get as much fact-based and researched-based information as possible. Personally, my goal is to act ethically with long-term vision in an area where there's a lot of fog and hype. The entire field of genomics and longevity is on the verge of a major revolution in my opinion - and that includes the on-going Methuselah Fly research.

I appreciate your response as well. I will add your product to a growing list of inceasingly promising treatments for Alzheimer's disease that I need to keep an eye on: everything from Feru-guard (ferulic acid in rice bran and garden angelica)

The problem with things that don't work is that it leads people to believe that nothing works. A certain amount of skepticism is helpful but blanket skepticism is decidely unhelpful. Just as there are multiple causes for Alzheimer's disease there are multiple treatments. And just as all the causes results in oxidative and nitrostative damage to the brain, all the treatment partially reverse this damage.